DM1-SMCC
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MedKoo CAT#: 407202

CAS#: 1228105-51-8

Description: DM1-SMCC is DM1 with a reactive linker SMCC, which can react with antibody to make antibody drug conjugate. DM1 is an antibody-conjugatable maytansinoid that was developed to overcome systemic toxicity associated with maytansine and to enhance tumor-specific delivery. DM1 binds at the tips of microtubules and suppresses the dynamicity of microtubules.

Chemical Structure

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DM1-SMCC
CAS# 1228105-51-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407202
Name: DM1-SMCC
CAS#: 1228105-51-8
Chemical Formula: C51H66ClN5O16S
Exact Mass: 1,071.39
Molecular Weight: 1,072.620
Elemental Analysis: C, 57.11; H, 6.20; Cl, 3.30; N, 6.53; O, 23.87; S, 2.99

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2450 Ready to ship
1g USD 3850 Ready to ship
2g USD 5850 Ready to ship
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Synonym: DM1-SMCC; DM1 SMCC; DM1SMCC. SMCC-DM1.

IUPAC/Chemical Name: 2,5-dioxopyrrolidin-1-yl 4-((3-((3-(((2S)-1-(((14S,16S,33S,2R,4R,10E,12Z,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl)oxy)-1-oxopropan-2-yl)(methyl)amino)-3-oxopropyl)thio)-2,5-dioxopyrrolidin-1-yl)methyl)cyclohexane-1-carboxylate

InChi Key: IADUWZMNTKHTIN-IOBAKXROSA-N

InChi Code: InChI=1S/C51H66ClN5O16S/c1-27-10-9-11-37(69-8)51(67)25-35(70-49(66)53-51)28(2)45-50(4,72-45)38(24-42(61)55(6)33-21-31(20-27)22-34(68-7)44(33)52)71-47(64)29(3)54(5)39(58)18-19-74-36-23-43(62)56(46(36)63)26-30-12-14-32(15-13-30)48(65)73-57-40(59)16-17-41(57)60/h9-11,21-22,28-30,32,35-38,45,67H,12-20,23-26H2,1-8H3,(H,53,66)/b11-9-,27-10+/t28-,29+,30?,32?,35+,36?,37-,38-,45?,50+,51+/m1/s1

SMILES Code: C[C@@H]1[C@@H]2C[C@](NC(O2)=O)(O)[C@H](OC)/C=C\C=C(C)\CC3=CC(N(C)C(C[C@@H](OC([C@@H](N(C(CCSC(C(N4CC5CCC(C(ON6C(CCC6=O)=O)=O)CC5)=O)CC4=O)=O)C)C)=O)[C@@]7(C)C1O7)=O)=C(Cl)C(OC)=C3

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: SMCC-DM1 (DM1-SMCC) is a drug-linker conjugate composed of a potent microtubule-disrupting agent DM1 and a linker SMCC to make antibody drug conjugate (ADC).
In vitro activity: In particular, the metabolic fate in cells of huC242-maytansinoid conjugates containing either a disulfide linker (huC242-SPDB-DM4) or a thioether linker (huC242-SMCC-DM1) was examined. The disulfide-linked antibody-maytansinoid conjugate, huC242-SPDBDM4, and the thioether-linked conjugate, huC242-SMCC-DM1, were first assayed for their cytotoxic potency against antigen-positive COLO 205 cells and antigen-negative Namalwa cells (both sensitive to maytansine with IC50 values of ∼30 to 60 pmol/L for both cell lines) using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)–based assay. The conjugates displayed similar potencies with IC50 values of 40 pmol/L against COLO 205 cells and 20 to 80 nmol/L against Namalwa cells upon a 4-day exposure of the cells to the conjugates ( Fig. 1A ). To examine the fate of the maytansinoid drug upon incubation of target cells with an antibody-maytansinoid conjugate, conjugates with maytansinoids were prepared that were 3H-labeled at the C-20 methoxy group (see Fig. 5). Radiolabeled maytansinoid conjugates, huC242-SPDB-[3H]DM4 (250 mCi/mmol) and huC242-SMCC-[3H]DM1 (214 mCi/mmol), exhibit in vitro cytotoxicities similar to nonradiolabeled conjugate samples (data not shown). The two major metabolites, S-methyl-DM4 and lysine-Nε-SMCC-DM1, were synthesized and tested for their in vitro cytotoxicity against COLO 205 cells and Namalwa cells. Lysine-Nε-SMCC-DM1 was ∼105-fold less potent against both cell lines with an IC50 value of 0.1 μmol/L (data not shown). Accumulation of the lysine-Nε-SMCC-DM1 metabolite from the noncleavable conjugate is coincident with the observed formation of the potent S-methyl-DM4, DM4, and lysine-Nε-SPDB-DM4 from the cleavable conjugate. This suggests that the lysineNε-SMCC-DM1 metabolite is as potent as the metabolites from the cleavable conjugate when delivered intracellularly and that all of the maytansinoid metabolites are active when produced in the cell. Cancer Res. 2006 Apr 15;66(8):4426-33. https://pubmed.ncbi.nlm.nih.gov/16618769/
In vivo activity: The antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells were investigated in vitro and in vivo. The in vivo activity of BT062SPDB-DM4, BT062-SMCC-DM1, and BT062-SPP-DM was examined in murine MM cell xenograft model of human and severe combined immunodeficient (SCID) mice bearing implant bone chips injected with human MM cells (SCID-hu model). The in vivo efficacy of nBT062-SPDB-DM4, nBT062-SMCC-DM1, and nBT062-SPP-DM1 was next evaluated in SCID mice bearing established CD138-positive MOLP-8 human MM cells. A single i.v. administration of the immunoconjugates caused significant dose-dependent tumor growth inhibition and tumor regression at concentrations that were well tolerated, evidenced by stable body weight. nBT062SPDB-DM4 was the most active conjugate tested in this model (Fig. 6A ). In addition, weekly dosing of the nBT062-SMCC-DM1 (six doses of 13.8 μg/kg) completely blocked tumor growth during the dosing period (Supplementary Fig. S6A). In summary, nBT062-SMCC-DM1, nBT062-SPDB-DM4, and nBT062-SPP-DM1 have in vitro and in vivo antitumor activity against CD138positive MM cells and can overcome the protective effects of cytokines and BMSCs Clin Cancer Res. 2009 Jun 15;15(12):4028-37. https://pubmed.ncbi.nlm.nih.gov/19509164/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 93.23

Preparing Stock Solutions

The following data is based on the product molecular weight 1,072.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009 Jun 15;15(12):4028-37. doi: 10.1158/1078-0432.CCR-08-2867. Epub 2009 Jun 9. PMID: 19509164. 2. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blättler WA. Antibodymaytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006 Apr 15;66(8):4426-33. doi: 10.1158/0008-5472.CAN-05-4489. PMID: 16618769. 3. Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, Singh R. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92. doi: 10.1021/bc900315y. PMID: 19891424. 4. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009 Jun 15;15(12):4028-37. doi: 10.1158/1078-0432.CCR-08-2867. Epub 2009 Jun 9. PMID: 19509164.
In vitro protocol: 1. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009 Jun 15;15(12):4028-37. doi: 10.1158/1078-0432.CCR-08-2867. Epub 2009 Jun 9. PMID: 19509164. 2. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blättler WA. Antibodymaytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006 Apr 15;66(8):4426-33. doi: 10.1158/0008-5472.CAN-05-4489. PMID: 16618769.
In vivo protocol: 1. Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, Singh R. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92. doi: 10.1021/bc900315y. PMID: 19891424. 2. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009 Jun 15;15(12):4028-37. doi: 10.1158/1078-0432.CCR-08-2867. Epub 2009 Jun 9. PMID: 19509164.

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1: Sun Y, Liang Y, Dai W, He B, Zhang H, Wang X, Wang J, Huang S, Zhang Q. Peptide-Drug Conjugate-Based Nanocombination Actualizes Breast Cancer Treatment by Maytansinoid and Photothermia with the Assistance of Fluorescent and Photoacoustic Images. Nano Lett. 2019 May 8;19(5):3229-3237. doi: 10.1021/acs.nanolett.9b00770. Epub 2019 Apr 11. PubMed PMID: 30957499.

2: Shao S, Tsai MH, Lu J, Yu T, Jin J, Xiao D, Jiang H, Han M, Wang M, Wang J. Site-specific and hydrophilic ADCs through disulfide-bridged linker and branched PEG. Bioorg Med Chem Lett. 2018 May 1;28(8):1363-1370. doi: 10.1016/j.bmcl.2018.03.005. Epub 2018 Mar 3. PubMed PMID: 29559276.

3: Sun X, Ponte JF, Yoder NC, Laleau R, Coccia J, Lanieri L, Qiu Q, Wu R, Hong E, Bogalhas M, Wang L, Dong L, Setiady Y, Maloney EK, Ab O, Zhang X, Pinkas J, Keating TA, Chari R, Erickson HK, Lambert JM. Effects of Drug-Antibody Ratio on Pharmacokinetics, Biodistribution, Efficacy, and Tolerability of Antibody-Maytansinoid Conjugates. Bioconjug Chem. 2017 May 17;28(5):1371-1381. doi: 10.1021/acs.bioconjchem.7b00062. Epub 2017 Apr 13. PubMed PMID: 28388844.

4: Ponte JF, Sun X, Yoder NC, Fishkin N, Laleau R, Coccia J, Lanieri L, Bogalhas M, Wang L, Wilhelm S, Widdison W, Pinkas J, Keating TA, Chari R, Erickson HK, Lambert JM. Understanding How the Stability of the Thiol-Maleimide Linkage Impacts the Pharmacokinetics of Lysine-Linked Antibody-Maytansinoid Conjugates. Bioconjug Chem. 2016 Jul 20;27(7):1588-98. doi: 10.1021/acs.bioconjchem.6b00117. Epub 2016 Jun 20. PubMed PMID: 27174129.

5: Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016 Jul;107(7):1039-46. doi: 10.1111/cas.12966. Epub 2016 Jun 22. PubMed PMID: 27166974; PubMed Central PMCID: PMC4946713.

6: Salomon PL, Singh R. Sensitive ELISA Method for the Measurement of Catabolites of Antibody-Drug Conjugates (ADCs) in Target Cancer Cells. Mol Pharm. 2015 Jun 1;12(6):1752-61. doi: 10.1021/acs.molpharmaceut.5b00028. Epub 2015 Mar 17. PubMed PMID: 25738394.

7: Goldmacher VS, Amphlett G, Wang L, Lazar AC. Statistics of the distribution of the abundance of molecules with various drug loads in maytansinoid antibody-drug conjugates. Mol Pharm. 2015 Jun 1;12(6):1738-44. doi: 10.1021/mp5007536. Epub 2015 Feb 17. PubMed PMID: 25635630.

8: Deckert J, Park PU, Chicklas S, Yi Y, Li M, Lai KC, Mayo MF, Carrigan CN, Erickson HK, Pinkas J, Lutz RJ, Chittenden T, Lambert JM. A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood. 2013 Nov 14;122(20):3500-10. doi: 10.1182/blood-2013-05-505685. Epub 2013 Sep 3. PubMed PMID: 24002446.

9: Kellogg BA, Garrett L, Kovtun Y, Lai KC, Leece B, Miller M, Payne G, Steeves R, Whiteman KR, Widdison W, Xie H, Singh R, Chari RV, Lambert JM, Lutz RJ. Disulfide-linked antibody-maytansinoid conjugates: optimization of in vivo activity by varying the steric hindrance at carbon atoms adjacent to the disulfide linkage. Bioconjug Chem. 2011 Apr 20;22(4):717-27. doi: 10.1021/bc100480a. Epub 2011 Mar 22. PubMed PMID: 21425776.

10: Oroudjev E, Lopus M, Wilson L, Audette C, Provenzano C, Erickson H, Kovtun Y, Chari R, Jordan MA. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol Cancer Ther. 2010 Oct;9(10):2700-13. doi: 10.1158/1535-7163.MCT-10-0645. PubMed PMID: 20937595; PubMed Central PMCID: PMC2976674.

11: Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, Singh R. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92. doi: 10.1021/bc900315y. PubMed PMID: 19891424.

12: Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009 Jun 15;15(12):4028-37. doi: 10.1158/1078-0432.CCR-08-2867. Epub 2009 Jun 9. PubMed PMID: 19509164.

13: Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blättler WA. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006 Apr 15;66(8):4426-33. PubMed PMID: 16618769.